The present invention relates to methods and apparatus for preparing liquid compounds for chemical and biological analysis, and more particularly, to equipment for dispensing minute volumes of liquid onto a substrate surface in an array in connection with drug discovery and diagnostic analysis.
As the field of biotechnology has developed, traditional techniques for analyzing chemical structures, such as the use of pipettes to manually deposit small amounts of liquid, have become impractical. Automated devices have been developed, for example, to permit parallel processing protocols for DNA diagnostics. In one form of such a device a matrix of individual pins is attached to a robotic arm. The spacing of the pins is sufficient to allow their terminal lower ends to be dipped into corresponding wells of a micro titer plate, thereby wetting the end of each pin with the sample liquid. The robotic arm then moves the pin matrix to the surface of a target substrate and contacts the end of each pin with the surface. The target substrate surface can either be flat or configured to provide a plurality of liquid receiving vessels or wells. The continual contact of the delicate pins to the substrate surface leads to wear which can introduce errors. U.S. Pat. No. No. 6,024,925 assigned to Sequenom, Inc. of San Diego discloses an improved pin replicator that uses individually spring biased hollow pins. However, the structure of the Sequenom pin replicator is relatively complex, unduly expensive and subject to mechanical failures.
It is therefore the primary object of the present invention to provide an improved pin replicator for dispensing minute volumes of liquid onto a substrate surface in an array in connection with drug discovery, diagnostic analysis, and other applications.
In accordance with the present invention, a pin replicator comprises a base plate, a plurality of pins reciprocable through corresponding holes in the base plate, and a free floating weight plate resting on top of the upper ends of the pins. The weight plate biases the pins toward their fully extended lowered positions. A cover attaches to the base plate, encloses the pins and weight plate and guides the weight plate during vertical movement thereof. The pin replicator can be moved downwardly toward a first micro titer plate so that a lower end of each of the pins contacts the sample liquid in the corresponding well a sufficient amount to pick up and retain a small quantity of the sample liquid due to surface tension. The weight plate serves to ensure co-planarity of the lower ends of the pins by pushing each pin downwardly to their fully extended lowered positions while allowing each pin to move upwardly should it contact an upper surface of the corresponding well of the first micro titer plate. The pin replicator can be moved upwardly away from the first micro titer plate and laterally to a position above a second micro titer plate. The pin replicator can then be moved downwardly toward the second micro titer plate so that the lower end of each of the pins is sufficiently close to a corresponding well of the second micro titer plate so that the small quantity of the sample liquid on the lower end of each of the pins contacts an upper surface of the corresponding well of the second micro titer plate. Thereafter the pin replicator can be moved upwardly away from the second micro titer plate and surface tension will cause a portion of the small quantity of the sample liquid previously carried by the lower end of each of the pins to remain in the corresponding well of the second micro titer plate.